Description
Thienamycin, the first of the carbapenems, was isolated from Streptomyces cattl eya. Because of its
extremely intense and broad-spectrum antimicrobial activity as well as its ability to inactivate β-lactamases,
it combines in one molecule the functional features of the best of the β-lactam antibiotics as well as the
β-lactamase inhibitors. It differs structurally in several important respects from the penicillins and
cephalosporins. The sulfur atom is not part of the 5-membered ring but, rather, has been replaced by a
methylene moiety at that position. Carbon is roughly half the molecular size of sulfur. Consequently, the
carbapenem ring system is highly strained and very susceptible to reactions cleaving the β-lactam bond. The
sulfur atom is now attached to C-3 as part of a functionalized side chain.
Uses
Carbapenems are beta-lactam antibiotics which have a broad spectrum of activity against many Gram-positive and Gram-negative aerobic and anaerobic organisms and are used for treating life-threatening serious infections not responding to standard antibiotic therapy.
Biosynthesis
The majority of carbapenems identified are produced by Streptomyces, but carbapenems have been shown to be produced by Photorhabdus and other Gram-negative bacteria such as Erwinia and Serratia. In Gram-negative bacteria, the biosynthesis of, and resistance to, the simple carbapenem molecule, 1-carbapen-2-em-3-carboxylic acid (Car), requires the products of the carABCDEFGH operon. The carABCDE genes encode the proteins required for Car biosynthesis from cellular precursors, while the carFGH genes encode for a mechanism that provides the bacteria with resistance to the antibiotic. In Erwinia and Serratia, the expression of the carABCDEFGH operon is controlled by quorum sensing (QS) and therefore only occurs during stationary phase when the bacteria are present at high cell densities.
Mechanism of action
Carbapenems bind PBPs disrupting the integrity of the bacterial cell wall thus causing cell death.
